Malaria: looking for selection signatures in the human PKLR gene region.

Abstract

The genetic component of susceptibility to malaria is both complex and multigenic and the better-known protective polymorphisms are those involving erythrocyte-specific structural proteins and enzymes. In vivo and in vitro data have suggested that pyruvate kinase deficiency, which causes a nonspherocytic haemolytic anaemia, could be protective against malaria severity in humans, but this hypothesis remains to be tested. In the present study, we conducted a combined analysis of Short Tandem Repeats (STRs) and Single Nucleotide Polymorphisms (SNPs) in the pyruvate kinase-encoding gene (PKLR) and adjacent regions (chromosome 1q21) to look for malaria selective signatures in two sub-Saharan African populations from Angola and Mozambique, in several groups with different malaria infection outcome. A European population from Portugal, including a control and a pyruvate kinase-deficient group, was used for comparison. Data from STR and SNP loci spread along the PKLR gene region showed a considerably higher differentiation between African and Portuguese populations than that usually found for neutral markers. In addition, a wider region showing strong linkage disequilibrium was found in an uncomplicated malaria group, and a haplotype was found to be associated with this clinical group. Altogether, this data suggests that malaria selective pressure is acting in this genomic region.

• Authors: Patrícia Machado, Rui Pereira, Ana Mafalda Rocha, Licínio Manco, Natércia Fernandes, Juliana Miranda, Letícia Ribeiro, Virgílio E do Rosário, António Amorim, Leonor Gusmão, Ana Paula Arez
• Journal: British journal of haematology (Br J Haematol) Vol. 149 Issue 5 Pg. 775-84 (Jun 2010) ISSN: 1365-2141 [Electronic] England
• PMID: 20377593 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Pyruvate Kinase

Topics

• Black People (genetics)
• Child
• Chromosomes, Human, Pair 1 (genetics)
• Gene Frequency
• Genetic Association Studies
• Genetic Predisposition to Disease
• Humans
• Linkage Disequilibrium
• Malaria, Falciparum (genetics)
• Microsatellite Repeats (genetics)
• Polymorphism, Single Nucleotide
• Pyruvate Kinase (deficiency, genetics)
• Selection, Genetic
• White People (genetics)